A Phase III clinical trial finds that patients with advanced, previously treated melanoma who received the monoclonal antibody ipilimumab lived 34 percent longer than those who received the gp100 peptide vaccine. The trial is the first randomized study to show an improvement in survival in advanced melanoma, where few treatment options exist.

"Over the last 30 years, randomized clinical trials have repeatedly failed to demonstrate an improvement in overall survival in patients with advanced melanoma. It's an extremely difficult disease to treat," said lead researcher Steven O'Day, M.D., chief of research and director of the melanoma program at The Angeles Clinic and Research Institute in Los Angeles, and clinical associate professor of medicine at the University of Southern California Keck School of Medicine. "These results are an exciting advance, both for patients with advanced melanoma and for the field of cancer immunology."

Ipilimumab is a monoclonal antibody that is administered intravenously. Unlike most treatments that target the cancer cell itself, ipilimumab represents a new class of drugs that activate the immune system's T cells, which then seek and destroy melanoma cells. Melanoma is one of the most deadly forms of cancer, and over the past three decades, melanoma incidence has climbed faster than any other cancer type.

In the study - which involved 125 centers internationally - Dr. O'Day and his colleagues compared the safety and effectiveness of ipilimumab plus placebo (137 patients), ipilimumab plus the gp100 vaccine (403), and the gp100 vaccine plus placebo (136) in patients with advanced (stage III/IV) melanoma. The gp100 vaccine, an experimental melanoma peptide vaccine also designed to stimulate T cells to attack melanoma cells, was used as a comparison group after previous studies showed it has modest anticancer activity and was superior to IL-2.

Those who received the vaccine alone lived a median of 6.5 months, which is comparable to placebo in past studies. The two arms receiving ipilimumab each lived a median of 10 months. Two-year survival was 24 percent among the patients who received ipilimumab and 22 percent among those who received combination treatment, versus 14 percent for patients who received the gp100 vaccine alone. The team also found better disease control with ipilimumab: after six months, the melanoma did not progress in nearly 30 percent of those receiving ipilimumab, compared to 11 percent with the vaccine alone.

Ipilimumab was generally well tolerated; however, between 10 percent and 14 percent of ipilimumab patients experienced sometimes severe side effects, such as rash and colitis, compared to about 3 percent of the vaccine patients.

Disclosures: Steven O'Day, Consultant or Advisory Role, Bristol-Meyers Squibb, Honoraria, Bristol-Meyers Squibb, Research Funding, Bristol-Meyers Squibb, Medarex; F. Hodi, Consultant or Advisory Role, Bristol-Meyers Squibb, Honoraria, Bristol-Meyers Squibb, Research Funding, Bristol-Meyers Squibb; David McDermott, Honoraria, Bristol-Meyers Squibb; Xiaoping Zhu, Employment/Leadership Position, Medarex, Inc., Stock Ownership, Bristol-Meyers Squibb; Michael Yellin, Employment/Leadership Position, Medarex, Inc., Stock Ownership, Bristol-Meyers Squibb, Medarex; Axel Hoos, Employment/Leadership Position, Bristol-Meyers Squibb, Stock Ownership, Bristol-Meyers Squibb; Walter Urba, Consultant or Advisory Role, Medarex, Inc.